The general area of interest in this research is the role of S-adenosylmethionine (AdoMet) in the biosynthesis of the polyamines putrescine, spermidine, and spermine. The polyamines are associated with proliferation of malignant as well as normal cells, and so increased knowledge concerning this pathway may lead to improved chemotherapeutic regimens. Principal findings in our laboratory during the second year of research include: (1)\our previous observation that AdoMet levels fluctuated during the cell cycle in murine erythroleukemia cells (MELC) has been extended to studies of the synthesis and amounts of polyamines. High AdoMet levels during S phase are accompanied by high concentrations of polyamines. This is consistent with our finding that polyamine synthesis is a major pathway for utilization of AdoMet; and (2)\limitation of methionine in the culture medium of MELC severely impairs polyamine synthesis. Similarly, restriction of methionine in diets of mice causes depletion of spermidine and spermine. During the third year of research we will be extending the studies on methionine restriction to include combination with inhibitors of polyamine synthesis in order to more effectively deplete cells or tissues or polyamines. (N)